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Thursday, October 24, 2013

Comparative oncology: How understanding and treating cancer in human and animal patients can benefit both

Beata Uvjari holds a Tasmanian Devil. Techniques developed to identify structural variation in cancer genomes may help solve the mystery of the Tasmanian Devil facial tumour disease.

Clinical
trials are common in the field of oncology – whether the patient is human or
animal. When conventional treatments fail, it is not uncommon for specialists
to reach for a novel or experimental drug, with informed consent of the patient
or pet owner of course. A number of my patients, under supervision of a veterinary
oncologist, have benefitted from access to such treatments. I know friends and family members of the human variety who have also benefitted because of such treatments. [I would hasten to add that not all patients benefit, and that decisions to use novel or experimental treatments need to be made carefully, on the best available evidence, weighing up the best interests of the patient. I also think it is important to manage expectations as some patients expect novel drugs to be a "wonderdrug". This is rarely the case].

Comparative
oncology is about sharing information between researchers working in the field
of human oncology, and those working with animals including veterinarians. Drugs
that attack cancer cells effectively in animals don’t always translate well to
humans – and vice versa – but they can.

SAT
interviewed Beata Uvjari, from the University of Sydney’s Comparative Oncology
Special Interest Group (CO-SIG) of the Cancer Research Network, a group
dedicated to maximising our knowledge by looking at cancer across all species.

What is comparative oncology?

Comparative
oncology is a multidisciplinary approach to exploit animal tumours as models in
order to increase our understanding of basic cancer mechanisms as well as their
treatment. Naturally occurring cancers of animals share biological, clinical
and therapeutic similarities to human cancers.

What is CO-SIG and who is involved?

The
Comparative Oncology Special Interest Group (CO-SIG) of the Cancer Research Network
(University of Sydney), hosted by the Faculty of Veterinary Science, was
established in 2012 as a multidisciplinary biomedical and diagnostic pipeline
linking clinicians, oncologists, epidemiologists and molecular researchers,
pursuing broad-based clinical and interdisciplinary approaches for an increased
understanding and treatment of cancer in all species.

The researchers and clinicians at the Faculty of Veterinary Sciences
investigate a range of spontaneously occurring animal cancers, which provide
excellent opportunities for clinical trials and biological studies and allow
early and humane testing of novel therapies.

This is an oral melanoma in a canine patient, anaesthetised for biopsy. This patient was treated surgically and with a novel vaccine under the guidance of a veterinary oncologist, and lived much longer (and much more comfortably) than he would otherwise.

What does the CO-SIG group actually do?

The
members of the CO-SIG propose to meet four times a year, and to invite speakers
from both animal and human cancer disciplines to showcase cancer research and
developments, and to increase awareness for collaboration across
disciplines. Students and members of the academic community are
encouraged to attend the meetings to foster networking and mentoring with
experienced researchers.

What are some of the current topical issues in
comparative oncology?

Some
of the most exciting topics of comparative oncology have been presented by our
recent speakers Prof. Tony Papenfuss (WEHI, Australia) and
Prof. Chand Khanna (NCI, USA). Prof. Papenfuss has
talked about the use of next generational sequencing technology
in analysing structural variation in cancer genomes and how computational
comparative genomics can help to solve the mystery of a contagious cancer, the
Tasmanian Devil Facial Tumour Disease.

Another
important link between human and animal cancers was presented by
Prof. Khanna who has
been using canine tumour cross-species genomics to uncover
targets linked to osteosarcoma progression.The
survival for newly diagnosed osteosarcoma, the most common type of bone cancer,
has not significantly changed over the last two decades; therefore
understanding the mechanisms of metastasis of this
aggressive paediatric cancer is urgently needed. Given the
accelerated biology of canine osteosarcomas, clinically affected pet dogs
provide opportunities to study the development and progression of pulmonary
metastasis.

A
parallel oligonucleotidearray analysis of human and
canine osteosarcomas could not only distinguish between the canine
and human diseases, but identified two potential target genes IL-8, SLC013,
which have been previously overlooked as diagnostic and therapeutic markers in
human osteosarcomas. Dr. Khanna’s results demonstrate the
importance of a comparative oncology approach to improve our understanding of
cancer biology and therapies.

Comparative
oncology also has an important and essential role in cancer drug development. Traditionally,
new drugs are evaluated in conventional preclinical models prior to human
clinical trials. Canine patients could provide an integrated approach to
translational drug development by being an intermediary between
conventional preclinical models and the human clinical trial – and pet dogs treated with trial drugs can
benefit from new treatments.

Use
of novel treatments in animal patients provides additional information, such as
dose, toxicity, pharmacokinetics and pharmacodynamics. [Ed - The decision to trial a drug on a canine patient is always undertaken with owner consent. No veterinarian or veterinary oncologist would advocate use of a drug on a trial basis that did not have a significant chance of benefitting the patient].

The
importance of an integrated approach to cancer drug development is also
highlighted by the work of our current speaker Dr. Chris Weir who has
developed a cancer vaccine which has the potential to improve life expectancy
and survival rates of patients suffering from brain tumours.

Dr.
Weir used cells from individual tumours, creating a unique and personalised
vaccine for each canine patient. The vaccine successfully slowed the growth of
tumours, helped prevent new ones from developing and prolonged the lives of the
canine patients, some diagnosed with advanced cancers. The success of the
canine trials opens up opportunities for human clinical studies, and gives hope
to both canine and human cancer sufferers

These
eminent studies provide strong evidence how a comparative approach to
cancer could lead to the identification of cancer-associated genes, help the
identification of environmental cancer risk factors, and most importantly, aid
the evaluation and development of novel cancer therapeutics for human and animal patients.

Who can become involved?

Anybody
who is interested in animal or human cancers, or just would like to learn about
cancer research, is welcome to join us, our meetings are open to public.

To
become formally involved with the Special Interest Group, one has to join
the University of Sydney’s Cancer Research Network:

Formal
membership is open to employees of the University of Sydney,
people employed by teaching hospitals and Institutes of
the University of Sydney, or people holding an academic title
award from the University of Sydney, who are active in the area
of cancer research. Membership is also open to postdoctoral fellows
and postgraduate research students enrolled at
the University of Sydney who are doing research in the area
of cancer. Further details can be found at:

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